Present situation and future of genetic profiling for prognosis and treatment

The Human Genome Project was a major milestone in the history of medicine. Both the genetic information obtained and the technological advances that took place during this large multicenter effort have had enormous influence over all fields of medicine. For the field of prognostication and prediction in breast cancer, the major consequence was the development of technology that led to the simultaneous evaluation of gene expression for hundreds and, more recently, thousands of genes. In fact, recently launched gene arrays include the entire human genome. Thus, we have the opportunity to assess, in a small tumor sample, the expression profile of all known human genes. There are multiple technological platforms under evaluation for this purpose, and the results obtained with one cannot automatically be substituted for results obtained with another platform. Nevertheless, on the basis of several reports, it can be stated that gene expression profiling of human breast cancer provides valuable information in the following areas:1. Molecular classification of primary breast cancer2. Identification of multiple distinct prognostic subgroups3. Determination of expression level of several genes of interest (ER, PR, HER2, etc.)4. Identification of genetic networks5. Prediction of response to chemotherapyThe initial reports were based on small patient numbers that presented substantial statistical challenges for adequate estimation of end-points and to prevent frequent false-positive or false-negative results. More recent analyses have included several dozen and up to a few hundred patients. These reports provide greater statistical power and greater reliability. However, these reports still represent retrospective analyses of subsets of patients, and prospective validation is still sorely needed. Reports are beginning to appear comparing the performance of different platforms on the same tumor samples and considering the same end-points. The source of tumor material, the manner